Immune complexes (IC) are intricately involved in many human diseases. Descriptions of fundamental properties and mechanisms of immune complex catabolism would dramatically aid in understanding disease processes, in designing effective antibodies for therapeutic purpose and in understanding basic aspects of immune system homeostasis. However, in the past it has not been possible to develop immune complexes which are stable to experimental manipulation or of precisely-defined chemical and physical composition. Studies are outlined to prepare model immune complexes by covalently cross-linking monoclonal antibodies through their antigen-binding sites with a new class of bivalent affinity label. The resulting model immune complex dimers, trimers and oligomers are stable to experimental manipulations and of precisely defined chemical and physical structure. These model IC will be assessed with regard to their usefulness as representatives of native (natural) IC and used to validate a new model, presented in this application, which explains, in part the mechanisms resulting in enhanced clearance of IC from the circulation. The model predicts that immunoglobulin-linked oligosaccharides in the constant portions of antibody molecules are stabilized by the processes of antigen binding and become exposed as "flags" for clearance mechanisms. This model will be tested in vitro by measuring the degree of Ig-linked carbohydrate exposure based on glycosidase susceptibility and the degree of Ig-linked oligosaccharide stabilization based on changes in anisotropic motions of spin-labeled Ig sialic acids. To validate the model in vivo, the catabolic fates of model IC will be studied as a function of the class, affinity and carbohydrate composition of Ig involved in the IC. One very important advantage of the model IC described herein is that large (gram) quantities of homogeneous IC can and will be produced and used to study the role of circulating IC in de novo immunity to the complexed antigen. This unresolved question is fundamental in the development of diseases such as cancer or the vasculitis associated with vinyl chloride factory workers.